Current and Future Viral Load Technologies

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Current and Future Viral Load Technologies

• Susan A. Fiscus, Ph.D.
• University of North Carolina at Chapel Hill

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Disclosures

• Honoraria Organon Teknika, Gen-Probe, Roche,
  Abbott
• Free kits NucliSens, Roche, Gen-Probe,
  Perkin-Elmer, Cavidi, Siemans, Abbott, and
  Inverness

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Commercially Available FDA Cleared HIV-1 Viral
Load Assays
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Commercially Available Non-FDA Cleared Viral Load
Assays
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Advantages/Disadvantages

• PROS
• Most are very sensitive (down to 40-50 cp/ml
  limit of detection) Do we always need this
  level of sensitivity?
• Most recognize most of the Group M subtypes and
  some detect Group O, N and one also detects HIV-2
  Do we need this capability most of the time?
• Most are high throughput good for central
  reference labs
• Most work with dried blood spots
• CONS
• Most require large, expensive equipment, highly
  trained technical staff, and instrument
  maintenance
• Results not available for several days to weeks
  so there may be problems returning results to the
  clinician and patient
• We need an inexpensive POC viral test for
  district hospitals and rural clinics

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Where are the POC Viral Load Assays?

• David Kelso Northwestern (Abbott-based)
• Wave 80 (Siemans-based)
• Helen Lee - Diagnostics for the Real World, Inc
• Advanced Liquid Logic
• IQuums Liat (Lab in a tube)
• Inverness-Clondiag
• Others?

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Liat Quantitative POC HIV Assay

• 200 uL plasma sample input
• Limit of detection - 78 copies/mL of ARNA
  detected in 60 min assay
• Dynamic range 100 to 10 million cp/mL in 60 min
• Detects HIV-1 Groups M and O and HIV-2 viruses
  using SeraCares Subtype Infectivity Panel
• Comparative data with 30 clinical specimens
• Roche COBAS - 88.4 correlation coefficient
• Siemens Versant 92 correlation coefficient

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Retrospective Clinical Sample Tests
88.4 correlation coefficients 92.0
correlation coefficients
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IMIs CLONDIAG HIV Viral Load Point-of-Care
Test Allows to determine HIV load (HIV) in
fingerstick whole blood and plasma. Multiple
HIV-1 and HIV-2 targets are detected
simultaneously by a proprietary microarray real
time detection method. The test includes internal
controls for performance of nucleic acid
extraction, purification, amplification and
detection. The sample is applied directly onto
the test cartridge no sample manipulation,
metering, dilution, or mixing are required. The
cartridge is processed by a compact, battery
driven instrument (W20cmXL24cmXH14cm). The test
is planned to be in trials throughout 2010.
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IMI CLONDIAG HIV VL Test Data generated on 1 ml
of EDTA Plasma (COBAS Ampliprep/Taqman) versus
10 µl of Whole Blood (IMIs prototype assay)
Percentage of samples with detectable viral
load COBAS (1 ml plasma) 50 IMI VL (10 µl
blood) 66 all samples are from HIV-positive
donors specificity of both assays 1 (32
HIV-negative donors)
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Conclusions

• Any of the commercially available RNA assays are
  appropriate for centralized lab testing and most
  work with DBS, but make sure to select one that
  detects and accurately quantitates the subtypes
  of the region and have supply chain and
  instrument maintenance contracts in place
• The Cavidi assay may be appropriate for smaller
  district hospitals (Mine, et al, 2009)
• The p24 antigen assay does not appear sensitive
  enough for VL monitoring, though may be adequate
  for infant diagnosis
• POC assays are being developed but more work is
  needed including validation by independent
  laboratories and field testing

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Obstacles to Implementation

• Infrastructure (may not be needed for POC)
• Guidelines and consensus protocols
• Lack of trained laboratory personnel (less
  emphasis for POC)
• Training tools
• Monitoring and evaluation tools
• Supply management
• Data management
• External quality assurance (Proficiency testing)